RESUMEN
BACKGROUND AND OBJECTIVE: Tobacco use is associated with increased periodontal destruction in both cigarette smokers and smokeless tobacco users. Gingival keratinocytes are the first cells in contact with microbial and tobacco components and play a key role in the innate immune response to these agents. The objective of this study was to evaluate the effect of nicotine and bacterial lipopolysaccharide (LPS) alone and in combination on gingival keratinocyte production of interleukin-1 alpha (IL-1 alpha) and interleukin-8 (IL-8). MATERIAL AND METHODS: Gingival keratinocyte cultures were established from 10 healthy, non-tobacco-using subjects. The cells were stimulated for 24 h with 1 mum or 1 mm nicotine and/or 10 microg/mL Escherichia coli or Porphyromonas gingivalis LPS. Interleukin-1 alpha and IL-8 proteins were quantified using ELISAs. RESULTS: Compared with untreated cultures, 1 mm nicotine stimulated production of IL-1 alpha (p < 0.001); E. coli and P. gingivalis LPS increased IL-8 production (p = 0.0014 and p = 0.0232, respectively). A combination of nicotine and LPS produced the highest cytokine quantities. Amounts of IL-1 alpha and IL-8 following 1 mm nicotine and LPS exposure were significantly greater than in untreated cultures (p < 0.001). Interleukin-8 was also responsive to 0.1 mum nicotine combined with E. coli or P. gingivalis LPS compared with control cultures (p < 0.0001 and p = 0.0029, respectively). Both cytokines tended to be elevated following the combined treatment relative to nicotine or LPS treatment alone. CONCLUSION: These results demonstrate that nicotine and LPS differentially regulate IL-1 and IL-8 production by gingival keratinocytes. Combined treatment tended to elevate cytokine production further, which may have implications for the progression of periodontitis in tobacco users.
Asunto(s)
Encía/efectos de los fármacos , Interleucina-1alfa/análisis , Interleucina-8/análisis , Queratinocitos/efectos de los fármacos , Lipopolisacáridos/farmacología , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Sinergismo Farmacológico , Escherichia coli/fisiología , Encía/citología , Encía/inmunología , Humanos , Mediadores de Inflamación/farmacología , Queratinocitos/inmunología , Porphyromonas gingivalis/fisiología , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVE: Cytokines and chemokines play an important role in the pathogenesis of periodontal diseases. The objective of this study was to quantitatively assess the effect of initial periodontal therapy on gingival crevicular fluid levels of a comprehensive panel of cytokines and chemokines, including several less extensively studied mediators. MATERIAL AND METHODS: Clinical examinations were performed and gingival crevicular fluid samples obtained from six subjects with generalized severe chronic periodontitis prior to initial periodontal therapy and at re-evaluation (6-8 weeks). Four diseased and two healthy sites were sampled in each subject. Twenty-two gingival crevicular fluid mediators were examined using a multiplex antibody capture and detection platform. Statistical analyses were performed by fitting mixed effects linear models to log-transformed gingival crevicular fluid values. RESULTS: Gingival crevicular fluid interleukin (IL)-1alpha and IL-1beta were the only cytokines to differ in initially diseased vs. initially healthy sites. Following initial therapy, 13 of the 16 detectable cytokines and chemokines decreased significantly in diseased sites, including IL-1alpha, IL-1beta, IL-2, IL-3, IL-6, IL-7, IL-8, IL-12 (p40), CCL5/regulated on activation, normally T cell expressed and secreted (RANTES), eotaxin, macrophage chemotactic protein-1, macrophage inflammatory protein-1alpha and interferon-gamma. At healthy sites, only three of the 16 mediators were significantly altered following therapy. CONCLUSION: This is the first study, to our knowledge, to evaluate such an extensive panel of gingival crevicular fluid mediators within the same sample prior to and following initial therapy. The results confirm that periodontal therapy effectively reduces pro-inflammatory cytokines and chemokines, including less well-described mediators that may be important in initiation and progression of periodontitis. The multiplex assay will prove useful for future gingival crevicular fluid studies.
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Periodontitis Crónica/terapia , Citocinas/análisis , Líquido del Surco Gingival/química , Adulto , Anciano , Quimiocina CCL2/análisis , Quimiocina CCL3/análisis , Quimiocina CCL5/análisis , Quimiocinas/análisis , Quimiocinas CC/análisis , Estudios de Seguimiento , Hemorragia Gingival/terapia , Recesión Gingival/terapia , Humanos , Mediadores de Inflamación/análisis , Interferón gamma/análisis , Interleucina-12/análisis , Interleucina-1alfa/análisis , Interleucina-1beta/análisis , Interleucina-2/análisis , Interleucina-3/análisis , Interleucina-6/análisis , Interleucina-7/análisis , Interleucina-8/análisis , Persona de Mediana Edad , Pérdida de la Inserción Periodontal/terapia , Bolsa Periodontal/terapia , Proyectos PilotoRESUMEN
The digital revolution and growth of the Internet have led to many innovations in the area of electronic learning (e-learning). To survive and prosper, educators must be prepared to respond creatively to these changes. Administrators and information technology specialists at six dental schools and their parent institutions were interviewed regarding their opinions of the impact that e-learning will have on the future of dental education. Interview questions encompassed vision, rate of change, challenges, role of faculty, resources, enrolment, collaboration, responsibility for course design and content, mission and fate of the institution. The objective of this qualitative study was to sample the opinions of educational administrators and information technology specialists from selected US universities regarding the impact of e-learning on dental education to detect trends in their attitudes. Responses to the survey indicated disagreement between administrators and informational technology specialists regarding the rate of change, generation of resources, impact on enrolment, responsibility for course design and content, mission and fate of the university. General agreement was noted with regard to vision, challenges, role of faculty and need for collaboration.
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Actitud hacia los Computadores , Educación en Odontología/tendencias , Docentes de Odontología , Internet , Facultades de Odontología/tendencias , Instrucción por Computador/economía , Instrucción por Computador/tendencias , Educación en Odontología/economía , Educación en Odontología/métodos , Tecnología Educacional/economía , Tecnología Educacional/tendencias , Humanos , Entrevistas como Asunto , Facultades de Odontología/economía , Estados UnidosRESUMEN
This study examines differences between cultures of normal human oral epithelial cells and two squamous cell carcinoma cell lines (SCC15 and SCC25) in the expression of structural proteins, adhesion molecules, plasma membrane lipid composition, and intercellular junctions. Based on immunocytochemistry, most normal cell cultures appeared to express more E-cadherin, integrin beta-1, cytokeratin (CK) 14, CK19, and involucrin than SCC cultures. By Western blot analysis, normal cultures expressing high levels of E-cadherin also expressed high levels of involucrin and low levels of CK19. Both SCC cultures demonstrated lower expression of E-cadherin and involucrin, whereas only SCC15 cells showed high levels of CK19. Expression of beta-catenin, an E-cadherin associated protein with potential oncogene function, did not vary among normal and SCC cells. Proportions of saturated fatty acids quantified by thin layer chromatography were higher in the normal cell cultures, than in both SCC cell lines. No morphological differences were evident by transmission electron microscopy (TEM) between normal and SCC cell-cell intercellular junctions. Although no quantitation was attempted, observation suggested that normal cells form more intercellular junctions (TEM observation) and larger intercellular bridges (SEM observation) compared to both SCC cell lines. Of the factors examined, main variations between cultures of normal oral epithelium and the two SCC cell lines examined include the expression of structural and adhesion proteins, lipid composition, and intercellular junctions. The extent of the differences varies according to the stage of terminal differentiation demonstrated by the normal cell cultures.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/química , Neoplasias de la Boca/química , Western Blotting/métodos , Cadherinas/análisis , Carcinoma de Células Escamosas/ultraestructura , Diferenciación Celular , Línea Celular Tumoral , Células Cultivadas , Ácidos Grasos/análisis , Encía/metabolismo , Encía/ultraestructura , Humanos , Inmunohistoquímica/métodos , Integrina beta1/análisis , Queratinocitos/metabolismo , Queratinocitos/ultraestructura , Queratinas/análisis , Microscopía Electrónica , Neoplasias de la Boca/ultraestructura , Precursores de Proteínas/análisisRESUMEN
This study evaluated the expression and regulation of beta-defensins DEFB-104 and the recently identified DEFB-105-14 in gingival keratinocytes. Keratinocytes from healthy subjects were exposed to cytokines, Escherichia coli lipopolysaccharide or Candida species. Total RNA was extracted and defensin expression analyzed by reverse transcription-polymerase chain reaction. Three patterns of expression were seen: no expression, constitutive expression and inducible expression. Constitutive mRNA expression was evident for DEFB-104, 107, 109, 111, and 112. DEFB-108 and 114 were induced by interleukin (IL)-1beta and Candida species. For DEFB-108 expression, synergism was observed when IL-1beta was combined with tumor necrosis factor-alpha or interferon-gamma. Downregulation of DEFB-109 occurred following treatment with Candida albicans. These findings suggest a role for multiple beta-defensins in response to oral infection. Further investigation is needed to better understand their function, both in terms of antimicrobial activities and contributions to innate and acquired immunity.
Asunto(s)
Antiinfecciosos/análisis , Encía/metabolismo , Queratinocitos/metabolismo , beta-Defensinas/análisis , Candida/fisiología , Candida albicans/fisiología , Citocinas/farmacología , Regulación hacia Abajo , Escherichia coli , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Humanos , Interferón gamma/farmacología , Interleucina-1/farmacología , Lipopolisacáridos/farmacología , ARN Mensajero/análisis , Factor de Necrosis Tumoral alfa/farmacología , beta-Defensinas/genéticaRESUMEN
Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease in the horse most commonly caused by Sarcocystis neurona. The domestic cat (Felis domesticus) is an intermediate host for S. neurona. In the present study, nine farms, known to have prior clinically diagnosed cases of EPM and a resident cat population were identified and sampled accordingly. In addition to the farm cats sampled, samples were also collected from a mobile spay and neuter clinic. Overall, serum samples were collected in 2001 from 310 cats, with samples including barn, feral and inside/outside cats. Of these 310 samples, 35 were from nine horse farms. Horse serum samples were also collected and traps were set for opossums at each of the farms. The S. neurona direct agglutination test (SAT) was used for both the horse and cat serum samples (1:25 dilution). Fourteen of 35 (40%) cats sampled from horse farms had circulating S. neurona agglutinating antibodies. Twenty-seven of the 275 (10%) cats from the spay/neuter clinic also had detectable S. neurona antibodies. Overall, 115 of 123 (93%) horses tested positive for anti-S. neurona antibodies, with each farm having greater than a 75% exposure rate among sampled horses. Twenty-one opossums were trapped on seven of the nine farms. Eleven opossums had Sarcocystis sp. sporocysts, six of them were identified as S. neurona sporocysts based on bioassays in gamma-interferon gene knockout mice with each opossum representing a different farm. Demonstration of S. neurona agglutinating antibodies in domestic and feral cats corroborates previous research demonstrating feral cats to be naturally infected, and also suggests that cats can be frequently infected with S. neurona and serve as one of several natural intermediate hosts for S. neurona.
Asunto(s)
Enfermedades de los Gatos/epidemiología , Vectores de Enfermedades , Encefalomielitis/veterinaria , Enfermedades de los Caballos/epidemiología , Zarigüeyas/parasitología , Sarcocistosis/veterinaria , Pruebas de Aglutinación/veterinaria , Animales , Animales Domésticos , Animales Salvajes , Anticuerpos Antiprotozoarios/sangre , Bioensayo/veterinaria , Enfermedades de los Gatos/parasitología , Gatos , Reservorios de Enfermedades/veterinaria , Encefalomielitis/epidemiología , Encefalomielitis/parasitología , Femenino , Enfermedades de los Caballos/parasitología , Caballos , Interacciones Huésped-Parásitos , Masculino , Ratones , Músculo Esquelético/parasitología , Ohio/epidemiología , Sarcocystis/inmunología , Sarcocystis/aislamiento & purificación , Sarcocistosis/epidemiología , Estudios SeroepidemiológicosRESUMEN
The severity of periodontal disease is dependent on a combination of host, microbial agent and environmental factors. One strong correlate related to periodontal disease pathogenesis is the immune status of the host. Here we show that human neutrophil peptide (HNP) defensins or human beta-defensins (HBD), co-administered intranasally with the antigen ovalbumin (OVA), induce unique immune responses that if used with microbial antigens may have the potential to hinder the pathogenesis of periodontal disease. C57BL/6 mice were immunized intranasally with phosphate buffered saline (PBS) containing 1 micro g HNP-1, HNP-2, HBD1 or HBD2 with and without 50 microg OVA. At 21 days, isotypes and subclasses of OVA-specific antibodies were determined in saliva, serum, nasal wash, bronchoalveolar lavage fluid, and fecal extracts. OVA-stimulated splenic lymphoid cell cultures from immunized mice were assessed for interferon (IFN)-gamma, Interleukin (IL)-4 and IL-10. In comparison with mice immunized with only OVA, HNP-1 and HBD2 induced significantly higher (P < 0.05) OVA-specific serum IgG, lower, but not significant, serum IgM and significantly lower (P < 0.05) IFN-gamma. In contrast, HNP-2 induced low OVA-specific serum IgG and higher, but not significant, serum IgM. HBD1 induced significantly higher (P < 0.05) OVA-specific serum IgG, higher, but not significant, serum IgM, and significantly higher (P < 0.05) IL-10. The elevated serum IgG subclasses contained IgG1 and IgG2b.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Defensinas/inmunología , Enfermedades Periodontales/prevención & control , Análisis de Varianza , Animales , Anticuerpos/análisis , Anticuerpos/sangre , Líquido del Lavado Bronquioalveolar/inmunología , Defensinas/farmacología , Heces/química , Femenino , Humanos , Inmunidad Activa/efectos de los fármacos , Inmunoglobulina G/análisis , Inmunoglobulina G/sangre , Inmunoglobulina M/análisis , Inmunoglobulina M/sangre , Interferón gamma/análisis , Interleucinas/análisis , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Ovalbúmina/inmunología , Enfermedades Periodontales/inmunología , Saliva/inmunología , alfa-Defensinas/inmunología , beta-Defensinas/inmunologíaRESUMEN
BACKGROUND: Beta-catenin, an E-cadherin-associated protein involved in cell-cell adhesion and signaling, has been hypothesized to translocate to the nucleus and activate transcription in several human cancers, including oral squamous cell carcinomas (OSCC). METHODS: In the present study, we analyzed the subcellular localization of beta-catenin in cultures of human oral normal and malignant (cell lines SCC15 and SCC25) keratinocytes and in 24 frozen samples of oral squamous cell carcinomas by a double-staining technique for nucleic acids and beta-catenin. Growth potential, as assessed by cell count at different time periods, was established for normal, SCC15 and SCC25 cell lines; oral squamous cell carcinomas were classified according to the histopathological and malignancy indexes. RESULTS: Beta-catenin localized at the plasma membrane in the normal and SCC15 cells, not in the SCC25 cells, where it localized mostly in the perinuclear and nuclear areas. In the growth assays, SCC25 cell lines proliferated faster than in normal and SCC15 cells over a period of 6 days (cell numbers were significantly different, P < 0.0001). Carcinoma sections showed a combination of membranous, cytoplasmic and, in few invading epithelial islands of two tumors, nuclear localization of beta-catenin. CONCLUSIONS: In oral squamous cell carcinomas, nuclear beta-catenin staining was observed only within invading islands of two carcinomas deep in the underlying connective tissue. On the basis of this study, we conclude that intranuclear beta-catenin does not appear to be a common finding in oral squamous cell carcinomas and that a clear association between intranuclear beta-catenin and histopathological and malignancy indexes in vivo could not be established.
Asunto(s)
Cadherinas/análisis , Carcinoma de Células Escamosas/ultraestructura , Proteínas del Citoesqueleto/análisis , Neoplasias de la Boca/ultraestructura , Fracciones Subcelulares/ultraestructura , Transactivadores/análisis , Adolescente , Adulto , Recuento de Células , Técnicas de Cultivo de Célula , División Celular , Membrana Celular/ultraestructura , Núcleo Celular/ultraestructura , Niño , Tejido Conectivo/ultraestructura , Células Epiteliales/ultraestructura , Encía/ultraestructura , Humanos , Queratinocitos/ultraestructura , Microscopía Confocal , Persona de Mediana Edad , Mucosa Bucal/ultraestructura , Células Tumorales Cultivadas , beta CateninaRESUMEN
This article reviews the effects of smoked and smokeless tobacco on periodontal status, including the impact of smoking on periodontal therapy and potential mechanisms for the adverse effects of tobacco on the periodontium. Approximately half of periodontitis cases have been attributed to either current or former smoking. Both cigar and cigarette smokers have significantly greater loss of bone height than nonsmokers, and there is a trend for pipe smokers to have more bone loss than nonsmokers. Unlike smokers, who experience widespread periodontal destruction, the most prevalent effects of smokeless tobacco are localized to the site of placement, in the form of gingival recession and white mucosal lesions. Smoking has an adverse effect on all forms of periodontal therapy, and up to 90 percent of refractory periodontitis patients are smokers. The pathogenesis of smoking-related periodontal destruction has been attributed to alterations in the microflora and/or host response. Some data indicates that smoking may increase levels of certain periodontal pathogens, but there is more evidence that smoking has a negative effect on host response, such as neutrophil function and antibody production. An encouraging finding is that periodontal disease progression slows in patients who quit smoking and that these individuals have a similar response to periodontal therapy as nonsmokers. The facts presented in this paper will assist dental health professionals in treatment-planning decisions and provide them with important information to share with patients who use tobacco products.
Asunto(s)
Enfermedades Periodontales/etiología , Plantas Tóxicas , Fumar/efectos adversos , Tabaco sin Humo/efectos adversos , Susceptibilidad a Enfermedades , Recesión Gingival/etiología , Humanos , Leucoplasia Bucal/etiología , Bolsa Periodontal/microbiología , Periodontitis/etiología , Periodoncio/fisiopatología , Cese del Uso de Tabaco , Estados Unidos , Cicatrización de HeridasRESUMEN
Epithelial beta-defensins are broad-spectrum cationic antimicrobial peptides that also act as chemokines for adaptive immune cells. In the human genome, all known defensin genes cluster to a <1 Mb region of chromosome 8p22-p23. To identify new defensin genes, the DNA sequence from a contig of large-insert genomic clones from the region containing human beta-defensin-2 (HBD-2) was analyzed for the presence of defensin genes. This sequence survey identified a novel beta-defensin, termed HBD-3. The HBD-3 gene contains two exons, is located 13 kb upstream from the HBD-2 gene, and it is transcribed in the same direction. A partial HBD-3 cDNA clone was amplified from cDNA derived from IL-1beta induced fetal lung tissue. The cDNA sequence encodes for a 67 amino acid peptide that is approximately 43% identical to HBD-2 and shares the beta-defensin six cysteine motif. By PCR analysis of two commercial cDNA panels, HBD-3 expression was detected in adult heart, skeletal muscle, placenta and in fetal thymus. From RT-PCR experiments, HBD-3 expression was observed in skin, esophagus, gingival keratinocytes, placenta and trachea. Furthermore, in fetal lung explants and gingival keratinocytes, HBD-3 mRNA expression was induced by IL-1beta. Additional sequence analysis identified the HE2 (human epididymis secretory protein) gene 17 kb upstream from the HBD-3 gene. One splice variant of this gene (HE2beta1) encodes a beta-defensin consensus cysteine motif, suggesting it represents a defensin gene product. HE2beta1 mRNA expression was detected in gingival keratinocytes and bronchial epithelia using RT-PCR analysis. The discovery of these novel beta-defensin genes may allow further understanding of the role of defensins in host immunity at mucosal surfaces.
Asunto(s)
Proteínas Portadoras , Genómica , Proteínas Recombinantes , beta-Defensinas/genética , Adulto , Secuencia de Aminoácidos , Antígenos de Superficie/genética , Secuencia de Bases , Mapeo Contig , ADN/química , ADN/genética , Exones , Femenino , Feto/metabolismo , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Genes/genética , Biblioteca Genómica , Glicopéptidos/genética , Glicoproteínas , Humanos , Intrones , Masculino , Datos de Secuencia Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Distribución Tisular , Proteínas de Transporte VesicularRESUMEN
BACKGROUND: Systemic disease and hormonal changes have been implicated as complicating factors for periodontal disease. Diabetes has been identified as a risk factor for periodontal disease, and diabetics can experience periodontal destruction at an earlier age than non-diabetic individuals. Increased hormone levels during pregnancy can contribute to increased gingival inflammation. The purpose of this study was to examine the association of type 1 diabetes mellitus (DM) on the periodontal status of pregnant women. METHODS: Thirty-three (13 diabetic and 20 non-diabetic) subjects, 20 to 39 weeks gestation, participated in this study. The mean age of the diabetics and non-diabetics was 28.5 +/- 7.1 (SD) and 27.0 +/- 7.3 years, respectively. The following parameters were assessed at Ramfjord's reference teeth: plaque index (PI), gingival inflammation (GI), probing depth (PD), gingival margin (GM) location, and clinical attachment level (CAL). RESULTS: Diabetic subjects had significantly (P<0.001) higher PI (1.48 +/- 0.69) and GI (1.77 +/- 0.44) scores than non-diabetics (PI = 0.63 +/- 0.38; GI = 0.93 +/- 0.48). Mean PD for diabetics (2.95 +/- 0.69 mm) was significantly different (P<0.024) from that of non-diabetics (2.44 +/- 0.32 mm). Although mean GM location was coronal to the cemento-enamel junction (CEJ) in both groups, gingival margins were at a more apical position (P<0.001) in the diabetics (-0.20 +/- 1.24 mm) compared to non-diabetics (-1.76 +/- 0.53 mm). Mean CAL values also varied significantly (P<0.001) between diabetics (2.60 +/- 1.54 mm) and non-diabetics (0.68 +/- 0.65 mm). Significant differences were seen for GI (P<0.001), PD (P=0.005), GM location (P<0.001), and CAL (P<0.001) when assessing the effect of diabetes and controlling for plaque. When assessing the effect of plaque and controlling for diabetes, the only significant difference was GI (P=0.001). CONCLUSIONS: The results of this study demonstrate that periodontal inflammation and destruction are increased in pregnant diabetics as compared to non-diabetic pregnant patients. These findings may have implications for diabetic control and, hence, maternal and fetal outcomes in pregnant diabetic patients.
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Diabetes Mellitus Tipo 1/complicaciones , Enfermedades Periodontales/clasificación , Complicaciones del Embarazo , Embarazo en Diabéticas , Adulto , Análisis de Varianza , Índice de Placa Dental , Femenino , Encía/patología , Recesión Gingival/clasificación , Gingivitis/clasificación , Humanos , Pérdida de la Inserción Periodontal/clasificación , Enfermedades Periodontales/etiología , Índice Periodontal , Bolsa Periodontal/clasificación , Embarazo , Factores de Riesgo , Método Simple Ciego , Estadística como Asunto , Cuello del Diente/patologíaRESUMEN
BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.
Asunto(s)
Antibacterianos/uso terapéutico , Minociclina/uso terapéutico , Periodontitis/tratamiento farmacológico , Administración Tópica , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Cápsulas , Terapia Combinada , Intervalos de Confianza , Raspado Dental , Femenino , Estudios de Seguimiento , Hemorragia Gingival/tratamiento farmacológico , Hemorragia Gingival/terapia , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/efectos adversos , Oportunidad Relativa , Pérdida de la Inserción Periodontal/tratamiento farmacológico , Pérdida de la Inserción Periodontal/terapia , Bolsa Periodontal/tratamiento farmacológico , Bolsa Periodontal/terapia , Periodontitis/terapia , Vehículos Farmacéuticos , Seguridad , Factores Sexuales , Fumar , Resultado del TratamientoRESUMEN
beta-Defensins are cationic peptides with broad-spectrum antimicrobial activity that are produced by epithelia at mucosal surfaces. Two human beta-defensins, HBD-1 and HBD-2, were discovered in 1995 and 1997, respectively. However, little is known about the expression of HBD-1 or HBD-2 in tissues of the oral cavity and whether these proteins are secreted. In this study, we characterized the expression of HBD-1 and HBD-2 mRNAs within the major salivary glands, tongue, gingiva, and buccal mucosa and detected beta-defensin peptides in salivary secretions. Defensin mRNA expression was quantitated by RNase protection assays. HBD-1 mRNA expression was detected in the gingiva, parotid gland, buccal mucosa, and tongue. Expression of HBD-2 mRNA was detected only in the gingival mucosa and was most abundant in tissues with associated inflammation. To test whether beta-defensin expression was inducible, gingival keratinocyte cell cultures were treated with interleukin-1beta (IL-1beta) or bacterial lipopolysaccharide (LPS) for 24 h. HBD-2 expression increased approximately 16-fold with IL-1beta treatment and approximately 5-fold in the presence of LPS. Western immunoblotting, liquid chromatography, and mass spectrometry were used to identify the HBD-1 and HBD-2 peptides in human saliva. Human beta-defensins are expressed in oral tissues, and the proteins are secreted in saliva; HBD-1 expression was constitutive, while HBD-2 expression was induced by IL-1beta and LPS. Human beta-defensins may play an important role in the innate defenses against oral microorganisms.
Asunto(s)
Antiinfecciosos/metabolismo , Mucosa Bucal/metabolismo , Biosíntesis de Proteínas , Glándulas Salivales/metabolismo , beta-Defensinas , Células 3T3 , Animales , Células Cultivadas , Fraccionamiento Químico , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Defensinas , Electroforesis Capilar , Regulación de la Expresión Génica , Encía/citología , Humanos , Queratinocitos/citología , Espectrometría de Masas , Ratones , Proteínas/genéticaRESUMEN
BACKGROUND: The clinical significance of incomplete pancreas divisum (IPD) has not been fully described. In this study we report the clinical presentation and results of endoscopic treatment of the 32 (0.6%) patients with IPD seen at our center over a 10-year period. METHODS: The study population consisted of 24 women and 8 men (mean age 42 years, range 13 to 82 years). Ten (31%) patients presented with acute recurrent pancreatitis, 5 (16%) with chronic pancreatitis, and 3 (9%) with pancreatic type pain. Detailed history, laboratory tests, US, CT, and ERCP excluded other etiologies for their symptoms. The remaining 14 (44%) presented with biliary problems. The 18 symptomatic patients with IPD were treated as follows: 8 received dorsal duct stents, 3 underwent minor papilla endoscopic sphincterotomy and dorsal duct stent placement, 4 had minor papilla dilatation only, and 3 had ventral duct stents placed. RESULTS: Patients were then followed for recurrence of pancreatitis and pancreatic-type pain. Mean follow-up was 15.5 months (range 3 to 30 months). Six (60%) of the patients with acute recurrent pancreatitis and 4 (80%) with chronic pancreatitis benefitted from the endoscopic therapy. However, only 1 (33%) of the patients with pancreatic-type pain benefitted. CONCLUSION: The clinical presentation and response to endoscopic therapy of patients with ICP appeared to be similar to that of patients with complete pancreas divisum.
Asunto(s)
Dolor Abdominal/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Conductos Pancreáticos/anomalías , Pancreatitis/cirugía , Dolor Abdominal/diagnóstico por imagen , Dolor Abdominal/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dilatación Patológica/diagnóstico por imagen , Dilatación Patológica/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Conductos Pancreáticos/diagnóstico por imagen , Conductos Pancreáticos/cirugía , Pancreatitis/complicaciones , Pancreatitis/diagnóstico por imagen , Recurrencia , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
The p16 INK4A tumor suppressor gene participates in establishing and maintaining the malignant phenotype of a variety of cancer cell lines and primary tumors. Recently it has been observed that p16 expression is lost in oral cavity cancer cell lines in the presence of a normal intact gene. To examine the role of DNA methylation as an explanation for these findings, we analyzed the DNA methylation patterns of the p16 INK4A promoter in DNA isolated from primary cultures of normal human oral keratinocytes and squamous cell carcinoma (SCC-15) oral cancer cells using bisulfite genomic sequencing. Our results demonstrated striking differences in the methylation status of the 5' CpG island of the p16 gene between normal and cancer cells. Normal human oral keratinocytes showed practically no methylation of the p16 INK4A promoter, while SCC-15 oral cancer cells showed almost complete methylation in this region. These data implicate DNA methylation as a mechanism for transcriptional silencing of the p16 INK4A gene in oral cancer cells.
Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Metilación de ADN , Genes p16 , Neoplasias de la Boca/genética , Humanos , Queratinocitos/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Reacción en Cadena de la Polimerasa/métodos , Células Tumorales CultivadasRESUMEN
The purpose of this study was to investigate the histological changes following short-term smokeless tobacco application in humans. Sixteen smokeless tobacco-using subjects participated in this trial. Each subject had used at least 3 cans of snuff per week for the previous 2 yr and had an existing lesion at the site of habitual snuff placement. The experimental design included subject placement of moist snuff (University of Kentucky reference tobacco brand 1S3) at a new site in the mandibular arch. At either 2 or 7 d, biopsies were taken from the new lesions and from a non-placement site in the opposing arch. The volume density of inflammatory cells was determined by point counting. Keratin and epithelial thickness were evaluated by digitizing morphometry. Data were analyzed by repeated measures analysis of variance. In 7-d lesions, increased keratin thickness was observed at the new sites compared to the non-placement sites (p = 0.05). Increased volume density of fibroblasts (p = 0.027) and decreased volume densities of macrophages (p = 0.0083) and mast cells (p = 0.05) were observed at 2 d in new versus non-placement sites. Clinically, the new sites showed erythema, erythema plus ulceration, or white striations. This study demonstrated histological and clinical changes at new snuff placement sites in as few as 2-7 d, underscoring the rapidity of tissue alterations following snuff use.
Asunto(s)
Enfermedades de la Boca/patología , Mucosa Bucal/patología , Plantas Tóxicas , Tabaco sin Humo/efectos adversos , Adulto , Análisis de Varianza , Recuento de Células , Epitelio/patología , Eritema/etiología , Eritema/patología , Fibroblastos/patología , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Queratinas/análisis , Macrófagos/patología , Masculino , Mandíbula , Mastocitos/patología , Enfermedades de la Boca/etiología , Neutrófilos/patología , Úlceras Bucales/etiología , Úlceras Bucales/patologíaRESUMEN
This study examined clinical and inflammatory mediator parameters during the development of snuff-induced mucosal lesions. Nineteen smokeless tobacco (ST) users placed moist snuff at designated new placement sites over either a 2- or 7-day period. By day 2, the predominant clinical alteration was an erythematous reaction, and one-third of the subjects demonstrated white striations in combination with erythema or ulceration. By 7 days, 56% of the subjects displayed white striated lesions. Tissue concentrations (pg/mg) of IL-1beta were 4.6+/-1.6 at new placement sites as compared with 0.7+/-0.4 at control sites (P<0.05). PGE2 and IL-1alpha concentrations also were significantly higher (P<0.05) at new placement sites as compared with control sites (9.4+/-2.2 vs 4.1+/-0.7 and 6.2+/-1.3 vs 3.2+/-0.7, respectively). In view of the recognized role of PGE2 and IL-1 in immune and inflammatory functions, these mediators may play a role in the pathogenesis of clinical alterations at ST placement sites.
Asunto(s)
Enfermedades de la Boca/etiología , Mucosa Bucal/patología , Plantas Tóxicas , Tabaco sin Humo/efectos adversos , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/análisis , Adolescente , Adulto , Dinoprostona/análisis , Humanos , Interleucina-1/análisis , Masculino , Enfermedades de la Boca/inmunología , Enfermedades de la Boca/patología , Mucosa Bucal/química , Mucosa Bucal/inmunologíaRESUMEN
BACKGROUND AND STUDY AIMS: Approximately 2-7% of patients who have undergone previous removal of bile duct stones have recurrence often presenting as ascending cholangitis. The aim of this study was to identify the incidence, clinical presentation, and objective findings in this group of patients. Additionally, the effect of surveillance endoscopic retrograde cholangiopancreatography (ERCP) in preventing cholangitis, was studied. PATIENTS AND METHODS: Two thousand and ninety-six patients who underwent ERCP for cholelithiasis were studied with 45 of these patients being identified as having recurrent common bile duct stones. Of the 45, 13 had two or more recurrences without having any obvious predisposing factors. The mean age of the 13 patients was 57 years. The characteristics of 13 patients were reviewed, including sphincterotomy size, liver function tests, and contrast drainage time. RESULTS: All 13 patients with recurrent stones presented with ascending cholangitis. Stones were found to be soft, brown and accompanied by a large amount of sludge. The common bile duct in all 13 patients was noted to be dilated and had notable, widely patent sphincterotomes. There was significant delayed drainage in 77% of these patients. Yearly surveillance ERCPs were performed in the 13 patients, the incidence of acute cholangitis episodes per patient decreased from 2 to 0.6 with a four-year follow-up. CONCLUSION: In a subgroup of patients with multiple common bile duct stone recurrences, annual surveillance ERCP with stone removal decreases the incidence of recurrent episodes of ascending cholangitis as well as its associated morbidity and mortality.
Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Colangitis/prevención & control , Cálculos Biliares/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Colangitis/fisiopatología , Femenino , Cálculos Biliares/diagnóstico , Cálculos Biliares/fisiopatología , Cálculos Biliares/cirugía , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Recurrencia , Estudios RetrospectivosRESUMEN
BACKGROUND: Possible sources of post-ERCP pancreatitis were evaluated during a prospective, randomized, controlled study comparing different contrast media. METHODS: A total of 1979 patients were randomized and subdivided into groups during the study. Patients were grouped for comparison depending on the type of procedure performed during ERCP. Diagnostic patients studied with pancreatograms (Group I) were compared with other groups, specifically, those not studied with pancreatograms (Group IV). All patients had subjective and objective estimates of the difficulty in cannulation of both ducts. The incidence of postprocedural pancreatitis was compared between and within each group. RESULTS: In Group I there was a progressively higher incidence of pancreatitis with increased numbers of pancreatic duct injections. Patients with the highest (19.5%) frequency of pancreatitis received 10 or more injections into the pancreatic duct. Group I cases with difficult common bile duct cannulations had a higher frequency of post-ERCP pancreatitis (9.5%), as compared with the entire group (5.6%). CONCLUSIONS: There was a higher incidence of pancreatitis associated with increased manipulation around the papillary orifice, especially with multiple pancreatic duct injections. There was also a slightly higher incidence of post-ERCP pancreatitis in cases with difficult common bile duct cannulation. Endoscopists are encouraged to evaluate and develop safer cannulation techniques that minimize the number of injections into the pancreatic duct and enhance selective cannulation.
Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Medios de Contraste/efectos adversos , Pancreatitis/etiología , Cateterismo/efectos adversos , Medios de Contraste/administración & dosificación , Método Doble Ciego , Humanos , Incidencia , Inyecciones , Conductos Pancreáticos , Pancreatitis/epidemiología , Estudios Prospectivos , Análisis de RegresiónRESUMEN
Oral keratinocytes are the first cells in contact with tobacco components and are capable of producing various inflammatory mediators, including PGE2 and IL-1. The purpose of this study was to examine PGE2 and IL-1 concentrations in nicotine-exposed oral keratinocyte cultures. Gingival keratinocyte cultures were established from healthy gingival tissues obtained from 7 subjects. Cultures were divided into 4 groups exposed to serum free medium (control), 0.1 microM, 10 microM or 1 mM nicotine for 4, 24 or 48 h. Using enzyme-linked immunosorbent assays, PGE2 and IL-1 alpha were quantified in culture supernatants; IL-1 alpha and beta were also measured in lysed cells. A repeated measures analysis of variance was used to identify significant differences over time and treatment. Nicotine exposure did not significantly alter PGE2 levels at any given time period; however, PGE2 quantities declined significantly (p = 0.0001) over time. At both 24 and 48 h, IL-1 alpha concentrations in lysates from 1 mM nicotine-exposed cells were significantly (p < 0.01) greater than those for all other treatments. Interleukin-1 alpha quantities also declined significantly (p = 0.037) over time in the cultures. Interleukin-1 beta concentrations were elevated, albeit not significantly, in the 1 mM treated cells at 24 and 48 h. Cell viability, mass and counts were not affected by nicotine treatment; these parameters increased significantly (p < 0.005) over time. In summary, nicotine treatment significantly increased IL-1 alpha concentrations in cultured keratinocytes; however, PGE2 synthesis was not altered. Elevated IL-1 production by keratinocytes may have implications in tobacco-induced lesions, given the central role IL-1 plays in tissue response to injury.